01 Jul Aspirin and Lifestyle Changes May Modulate Colon Cancer Risk
MedicalResearch: What are the main findings of the study?
Dr. Truninger: In our study, we investigated the effect of lifestyle exposure on DNA methylation. We measured genome-wide promoter CpG methylation in 1092 normal colon biopsies from 546 healthy females. We observed that fewer CpGs acquired age-dependent methylation in users of aspirin and hormonal replacement therapy compared with nonusers, whereas more CpGs were affected in smokers and individuals with a body mass index > 25 compared with nonsmokers and less obese females. Half of the CpGs showing age-dependent methylation gain were hypermethylated in tissue of colorectal cancer. These loci gained methylation with a higher rate and were particularly susceptible to lifestyle exposure compared to age-only methylated CpGs. In addition, these CpGs were enriched for polycomb regions. Finally, all effects were different according to the anatomic location along the colon.
MedicalResearch: Were any of the findings unexpected?
Dr. Truninger: We were surprised by both the highly significant enrichment for polycomb regions and the higher median methylation change rate in CpGs being hypermethylated in colorectal cancer and showing age-dependent methylation gain in normal tissue as compared to sites displaying age-dependent methylation increase in normal tissue, but not hypermethylated in tumor tissue. Promoter CpG methylation (in)stability is not a universe phenomenon, but is modulated in a locus specific manner by both biological and lifestyle factors.
MedicalResearch: What should clinicians and patients take away from your report?
Dr. Truninger: Lifestyle factors that are well know modulaters of colorectal cancer risk have widespread effects on stability of gene promoter methylation in the aging colonic mucosa. These findings provide an important resource to understand the interplay between lifestyle exposure and aging of the colonic mucosa in the evolution of cancer methylomes. Our data suggest that regular aspirin use stabilizes DNA methylation at promoters of genes controlling critical cancer pathways.
MedicalResearch: What recommendations do you have for future research as a result of this study?
Dr. Truninger: Future studies have to further establish the interaction between lifestyle exposure and cancer-relevant promoter methylation changes to develop tailored preventive strategies, i.e., which individuals might have a benefit from cancer preventive aspirin use.
Modulation of Age- and Cancer-Associated DNA Methylation Change in the Healthy Colon by Aspirin and Lifestyle
Faiza Noreen, Martin Röösli, Pawel Gaj, Jakub Pietrzak, Stefan Weis, Patric Urfer, Jaroslaw Regula, Primo Schär, and Kaspar Truninger